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High-density polyethylene (HDPE) pipes have been continuously improved by the progress made by the resin industry and pipe manufacturers. Together with the advanced technology of welding equipment in terms of structure reliability and automations, HDPE pipes have been gradually applied to higher pressure level, bigger diameter, and thicker walls in operations which have become the preferred piping system for nuclear safety application in transporting cooling seawater. There are substantial differences in parameter settings when applying heat and force during different welding procedures, as well as the complicated evaluation methods for mechanical properties, which causes communication barriers between engineers and researchers. Thus, it is necessary to comprehensively study the welding procedures and evaluation methods to standardize the evaluation protocols in the industry. In this paper, based on the assumptions of temperature effect and molecular chain diffusion dynamics at the welding interface, the optimization of the welding procedure is proposed. Some well-established evaluation methods have been used for performance assessment and their feasibilities are discussed. The idea of creating crack along the weld interface is adopted as new method to evaluate the material ability of fracture resistance. Specimens with unilateral notch and weld interface crack are proposed and subjected for quasi-static axial tensile test. The fracture stress and fracture energy at the welding interface are used to differentiate the quality of the joint from different welding procedures. The fracture morphologies of the weld interface are analyzed. A complete picture is drawn for the mechanical fracture resistance of the weld interface. The method used in this paper can be corelated to the pipeline design conditions, therefore could be applied to the real-time engineering applications. Moreover, the evaluation method proposed in this paper is simple, reliable, and easy to implement. • New specimens were designed to create fracture along the weld interface. • Weld interface properties were assessed to character the welding joint. • Method for welding procedure improvement was suggested. • Test results can be extended for design considerations in pipe applications. [ABSTRACT FROM AUTHOR]

The hydrogen transfer reaction is one of the main source of byproducts alkanes from methanol to aromatics resulting in reducing the aromatics selectivity. The hydrogen transfer reactions between two linear alkenes were systematically investigated utilizing the density functional theoretical method on clean H-ZSM-5 and [GaH]2+ from Ga modified ZSM-5. The results show that the [GaH]2+ species on Ga-ZSM-5 is favorable for the hydrogen transfer reaction in MTA. In addition, TOF of hydrogen transfer decreases with the increase of temperature on [GaH]2+ from Ga-ZSM-5. The insights in this work will be of great significance to understand the hydrogen transfer mechanism catalyzed by metal modified zeolite. [Display omitted] • [GaH]2+ is favorable for hydrogen transfer reaction. • The mechanisms of hydrogen transfer reactions on clean and Ga modified ZSM-5 are elucidated. • TOF of hydrogen transfer decreases with the increase of temperature on [GaH]2+ from Ga-ZSM-5. [ABSTRACT FROM AUTHOR]

The discovery of drug–drug interactions (DDIs) that have a translational impact among in vitro pharmacokinetics (PK), in vivo PK and clinical outcomes depends largely on the quality of the annotated corpus available for text mining. We have developed a new DDI corpus based on an annotation scheme that builds upon and extends previous ones, where an abstract is fragmented and each fragment is then annotated along eight dimensions, namely, focus, polarity, certainty, evidence, directionality, study type, interaction type and mechanism. The guideline for defining these dimensions has undergone refinement during the annotation process. Our DDI corpus comprises 900 positive DDI abstracts and 750 that are not directly relevant to DDI. The abstracts in corpus are separated into eight categories of DDI or non-DDI evidence: DDI with pharmacokinetic (PK) mechanism, in vivo DDI PK, DDI clinical, drug–nutrition interaction, single drug, not drug related, in vitro pharmacodynamic (PD) and case report. Seven annotators, three annotators with drug–interaction research experience and four annotators with less drug–interaction research experience independently annotated the DDI corpus, where two researchers independently annotated each abstract. After two rounds of annotations with additional training in between, agreement improved from (0.79, 0.96, 0.86, 0.70, 0.91, 0.65, 0.78, 0.90) to (0.93, 0.99, 0.96, 0.94, 0.95, 0.93, 0.96, 0.97) for focus, certainty, evidence, study type, interaction type, mechanisms, polarity and direction, respectively. The novice-level annotators improved from 0.83 to 0.96, while the expert-level annotators stayed in high performance with some improvement, from 0.90 to 0.96. In summary, we achieved 96% agreement among each pair of annotators with regard to the eight dimensions. The annotated corpus is now available to the community for inclusion in their text-mining pipelines. Database URL https://github.com/zha204/DDI-Corpus-Database/tree/master/DDI%20corpus [ABSTRACT FROM AUTHOR]

Phenolic compounds are naturally present as secondary metabolites in plant-based sources such as fruits, vegetables, and spices. They have received considerable attention for their antioxidant, anti-inflammatory, and anti-carcinogenic properties for protection against many chronic disorders such as neurodegenerative diseases, diabetes, cardiovascular diseases, and cancer. They are categorized into various groups based on their chemical structure and include phenolic acids, flavonoids, curcumins, tannins, and quinolones. Their structural variations contribute to their specific beneficial effects on human health. The antioxidant property of phenolic compounds protects against oxidative stress by up-regulation of endogenous antioxidants, scavenging free radicals, and anti-apoptotic activity. Protocatechuic acid (PCA; 3,4-dihydroxy benzoic acid) and protocatechuic aldehyde (PAL; 3,4-dihydroxybenzaldehyde) are naturally occurring polyphenols found in vegetables, fruits, and herbs. PCA and PAL are the primary metabolites of anthocyanins and proanthocyanidins, which have been shown to possess pharmacological actions including antioxidant activity in vitro and in vivo. This review aims to explore the therapeutic potential of PCA and PAL by comprehensively summarizing their pharmacological properties reported to date, with an emphasis on their mechanisms of action and biological properties. [ABSTRACT FROM AUTHOR]

Background: The aim of this retrospective study was to demonstrate that irAEs, specifically gastrointestinal and pulmonary, examined through International Classification of Disease (ICD) data leads to underrepresentation of true irAEs and overrepresentation of false irAEs, thereby concluding that ICD claims data are a poor approach to electronic health record (EHR) data mining for irAEs in immunotherapy clinical research. Methods: This retrospective analysis was conducted in 1,063 cancer patients who received ICIs between 2011 and 2017. We identified irAEs by manual review of medical records to determine the incidence of each of our endpoints, namely colitis, hepatitis, pneumonitis, other irAE, or no irAE. We then performed a secondary analysis utilizing ICD claims data alone using a broad range of symptom and disease-specific ICD codes representative of irAEs. Results: 16% (n = 174/1,063) of the total study population was initially found to have either pneumonitis 3% (n = 37), colitis 7% (n = 81) or hepatitis 5% (n = 56) on manual review. Of these patients, 46% (n = 80/174) did not have ICD code evidence in the EHR reflecting their irAE. Of the total patients not found to have any irAEs during manual review, 61% (n = 459/748) of patients had ICD codes suggestive of possible irAE, yet were not identified as having an irAE during manual review. Discussion: Examining gastrointestinal and pulmonary irAEs through the International Classification of Disease (ICD) data leads to underrepresentation of true irAEs and overrepresentation of false irAEs. [ABSTRACT FROM AUTHOR]

Chronic inflammation plays a crucial role in vascular calcification. However, only a few studies have revealed the mechanisms underlying the development of inflammation under high-phosphate conditions in chronic kidney disease (CKD) patients. Here, we show that inflammation resulting from the activation of the TGFBR1/TAK1 pathway is involved in calcification in CKD rats or osteogenic medium-cultured human aortic smooth muscle cells (HASMCs). Moreover, miR-135a-5p is demonstrated to be a key regulator of the TGFBR1/TAK1 pathway, which has been reported to be decreased in CKD rats. We further reveal that farnesoid X receptor (FXR) activation increases miR-135a-5p expression, thereby inhibiting the activation of the TGFBR1/TAK1 pathway, ultimately resulting in the attenuation of vascular inflammation and calcification in CKD rats. Our findings provide advanced insights into the mechanisms underlying the development of inflammation in vascular calcification, and evidence that FXR activation could serve as a therapeutic strategy for retarding vascular calcification in CKD patients. Li et al. investigate the mechanism behind vascular inflammation and calcification in chronic kidney disease (CKD) and show that inflammation is due to activation of the confirmed TGFBR1/TAK1 pathway, with miR-135a-5p as a key regulator. They further show that farnesoid X receptor activation upregulates miR-135a-5p which attenuates vascular inflammation and calcification in CKD rats. [ABSTRACT FROM AUTHOR]

Orphaned colonies of Cryptotermes domesticus readily produce replacement reproductives and continue propagation. In this study, we aimed to investigate the production and fecundity of neotenic reproductives in 5-year-old colonies of C. domesticus after orphaning. All 15 experimental colonies were successfully re-established by the neotenic reproductive pair. Three types of neotenic reproductives with various wing-bud lengths were observed: type I with micro wing buds, type II with short wing buds, and type III with long wing buds. Four patterns of pairs made up of these neotenics, namely, type I + type II, type I + type III, type II + type II, and type II + type III, exhibited reproductive capacities similar to those of the primary reproductive pair. We speculated that these neotenic reproductives were derived from various nymphal instars. The 5-year-old colonies had three instars of nymphs, with the majority being in the second instar, followed by the first. Thus, the combination of neotenic reproductives with short wing buds and micro wing buds was the dominant differentiation pathway of the orphaned colonies. After the removal of the original primary reproductive pair, the nymphs matured into neotenic reproductives and took over reproduction in the colony in 107.40 ± 15.18 days. This study highlights the importance of quarantine and routine inspection of wood, as well as the significance of early prevention and control of C. domesticus infestation in wood. Moreover, this study confirms the high differentiation and reproductive capacities of C. domesticus. [ABSTRACT FROM AUTHOR]

Aiming at the problem of water quality monitoring, this paper presents a method of biological water quality monitoring based on TLD (Tracking-Learning-Detection) framework and XGBoost (eXtreme Gradient Boosting). Firstly, under the framework of TLD, an independent tracking system is designed; TLD captures 3D coordinate information of fish based on video and calculates the behavior of fish movement parameters which can reflect the change of water quality via processing the coordinate information of the fish body. The data of coordinate information will be more prominent via the data processing. The integration of all built XGBoost water quality monitoring model which is based on characteristic parameters; the model was used to analyze and evaluate fish behavior parameters under unknown water quality to achieve the purpose of water quality monitoring. [ABSTRACT FROM AUTHOR]

Background/Aims: Studies have demonstrated that 2-dodecyl-6-methoxycyclohexa-2, 5-diene-1, 4-dione (DMDD), isolated from the roots of Averrhoa carambola L., has significant therapeutic potential for the treatment of diabetes. However, the protective effect of DMDD against pancreatic beta cell dysfunction has never been reported. We investigated whether DMDD protected against palmitic acid-induced dysfunction in pancreatic β-cell line Min6 cells by attenuating the inflammatory response and apoptosis and to shed light on its possible mechanism. Methods: Cell viability was assessed by CCK-8. Glucose-stimulated insulin secretion levels and inflammatory cytokines levels were examined by ELISA. Apoptosis was assessed by Annexin V-FITC/PI Flow cytometry assay, Hoechst 33342/PI double-staining assay, and Transmission electron microscopy assay. Relative quantitative real-time PCR and western blot were used to determine the expressions of genes and proteins. Results: Cell viability and glucose-stimulated insulin secretion levels were increased in DMDD-pretreated Min6 cells. DMDD inhibited inflammatory cytokines IL-6, TNF-α and MCP-1 generations in palmitic acid (PA)-induced Min6 cells. Moreover, DMDD protected against PA-induced Min6 cells apoptosis and the expression of Cleaved-Caspase-3, -8 and -9 were down-regulated and the Bcl-2/Bax ratio was increased in DMDD-pretreated Min6 cells. In addition, the expression of TLR4, MyD88 and NF-κB were down-regulated in DMDD-pretreated Min6 cells and TAK-242-pretreated group cells. Conclusions: DMDD protected Min6 cells against PA-induced dysfunction by attenuating the inflammatory response and apoptosis, and its mechanism of this protection was associated with inhibiting the TLR4-MyD88-NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Drug-drug interaction (DDI) information retrieval (IR) is an important natural language process (NLP) task from the PubMed literature. For the first time, active learning (AL) is studied in DDI IR analysis. DDI IR analysis from PubMed abstracts faces the challenges of relatively small positive DDI samples among overwhelmingly large negative samples. Random negative sampling and positive sampling are purposely designed to improve the efficiency of AL analysis. The consistency of random negative sampling and positive sampling is shown in the paper. Results: PubMed abstracts are divided into two pools. Screened pool contains all abstracts that pass the DDI keywords query in PubMed, while unscreened pool includes all the other abstracts. At a prespecified recall rate of 0.95, DDI IR analysis precision is evaluated and compared. In screened pool IR analysis using supporting vector machine (SVM), similarity sampling plus uncertainty sampling improves the precision over uncertainty sampling, from 0.89 to 0.92 respectively. In the unscreened pool IR analysis, the integrated random negative sampling, positive sampling, and similarity sampling improve the precision over uncertainty sampling along, from 0.72 to 0.81 respectively. When we change the SVM to a deep learning method, all sampling schemes consistently improve DDI AL analysis in both screened pool and unscreened pool. Deep learning has significant improvement of precision over SVM, 0.96 vs. 0.92 in screened pool, and 0.90 vs. 0.81 in the unscreened pool, respectively. Conclusions: By integrating various sampling schemes and deep learning algorithms into AL, the DDI IR analysis from literature is significantly improved. The random negative sampling and positive sampling are highly effective methods in improving AL analysis where the positive and negative samples are extremely imbalanced. [ABSTRACT FROM AUTHOR]

Lithium-sulfur (Li-S) battery possess the advantage of high specific energy but suffer from unstable cyclic performance due to the sluggish liquid-solid conversion kinetics causing severe lithium polysulfides (LiPS) shuttling. Designing multifunctional electrocatalysts with improved activity and abundant active sites to regulate the dynamics for sulfur electrochemistry is still a significant challenge. Herein, we proposed a thiourea assisted pyrolysis combined with hard template method to synthesize cobalt single atoms co-coordinated by N and S atoms embedded hollow carbon spheres (Co-NS-HCS) as a novel sulfur host. The Co-NS-HCS mainly consists of well-dispersed Co-N 3 S-C center sites where Co is co-bonded by N and S atoms. Systematical characterizations revealed that the Co-NS-HCS exhibit improved SRR electrocatalytic properties with higher exchange current density and larger electron transfer number than that of Co-N-HCS. When equipped in sulfur cathodes, the S@Co-NS-HCS exhibits superior rate performance (925 mAh g−1 at 2 C), long cycle stability (69.1% of capacity retention after 500 cycles at 1 C). Moreover, the assembled Li-S pouch type cell also exhibits competitive cyclic performance that work stably for 100 cycles at 0.1 C with a high capacity retention of 84.7%. This work furnishes a feasible scheme for the rational design of single atoms catalysts with improved electrocatalytic activity for sulfur cathodes based on the coordination environment regulation strategy. Cobalt single atoms co-coordinated by N and S atoms embedded hollow carbon spheres is synthesized as a highly efficient sulfur electrocatalyst to boost both the sulfur reduction and Li 2 S oxidation for advanced Li-S batteries with improved cyclic performance. [Display omitted] • Co single atoms coordinated by N/S are designed as efficient electrocatalysts. • The redox reaction kinetics of LiPS are boosted through S modulation. • The shuttle effect of LiPS is efficiently suppressed. • A high capacity retention of 84.7% is obtained in Li-S pouch cell. [ABSTRACT FROM AUTHOR]

The investigation about the uniaxial stretching behavior of two crystallized poly(L-lactide)s (PLLA) with the same degree of crystallinity but different crystalline morphologies was carried out by two dimensional Wide Angle X-ray Scattering (2D-WAXS) and Differential Scanning Calorimetry (DSC). The original lamellar blocks and the orientation induced fibrillar crystals coexist during stretching for both samples, and a mesophase is detected when the material is drawn at 65 °C. Larger elongation and hence higher crystal orientation can be obtained for the sample with nucleating agent which owns the thinner average lamellar thickness, whereas the lower melting point indicates the fibrillar crystals in this stretched sample are less perfect. Besides, higher draw temperature benefits the unfolding of chains in the original lamellae but can also decrease the chain orientation due to the enhanced chain relaxation. The original lamellar thickness is supposed to be the governing factor which determines the different crystalline structures under strain. [ABSTRACT FROM AUTHOR]

Key Clinical Message We report a comatose patient with severe neurological deficits who was without spontaneous language or movement. He had a good response to recombinant tissue plasminogen activator (rt PA) thrombolysis even though there were no detectable lesions on diffusion-weighted imaging ( DWI). DWI is very sensitive for diagnosing hyperacute ischemic stroke, and rt PA thrombolysis is the best treatment. However, rt PA thrombolysis in ischemic stroke patients without lesions on DWI has rarely been reported. [ABSTRACT FROM AUTHOR]

Objective The goal of present study was to examine the influence of demographic characteristics, lifestyle, and metabolic factors on pressure-induced pain threshold. Design and Setting The study population comprised 2,517 healthy men at second-phase recruitment of a population-based cohort in China. The pressure pain threshold ( PPT) at two locations, triceps and inguinal lines, was obtained using a digital pressure algometer. Education and occupation, as well as lifestyle factors, were self-reported in a face-to-face interview. Blood lipid and fasting glucose were measured as a routine healthy check-up program. Results A lower PPT was found among men with younger age, higher level of education, and non-manual occupation. In addition, men with central obesity and moderate leisure time physical exercise were more sensitive to muscle mechanical stimuli. PPT was significantly correlated with high-density lipoprotein cholesterol (β for triceps = 0.064, and β for inguinal lines = 0.052) in a multivariate linear regression model, after controlling for multiple variables. Elevated PPT was also found among subjects with hyperglycemia (both P for triceps and inguinal lines <0.001) and excess drinking ( P for triceps = 0.005). Conclusions It is important for physicians and researchers to consider these variables when evaluating pain sensitivity in clinic and in research. The underling mechanisms between these factors and pressure pain perception are worthy of further exploration. [ABSTRACT FROM AUTHOR]

Abstract: This study examined the effects and possible mechanisms of rifampin against acetaminophen-induced hepatotoxicity in mice. Rifampin significantly enhanced the biotransformation of acetaminophen, evidenced by the increase in p-aminophenol formation in rifampin-treated microsomes and the increase in plasma clearance rate of acetaminophen. Pretreatment with rifampin significantly decreased serum alanine transaminase (ALT) activities, aspartate transaminase (AST) activities and prevented severe liver necrosis following acetaminophen overdose. The contents and activities of microsomal drug-metabolizing enzyme were less affected in rifampin-pretreated mice in comparison to the animals treated with acetaminophen alone. Rifampin was capable of increasing glutathione (GSH) level and GSH reductase activity and reducing GSH depletion and the decrease in GSH reductase activity by acetaminophen in mice. In addition, it was found that the microsomal Ca2+-ATPase activity was not directly related to acetaminophen toxic species generated in the P450 enzyme system in vitro. These findings suggest that rifampin has species-specific effects on the liver against acetaminophen-induced hepatotoxicity in mice, which increase the level of GSH by promoting GSH regeneration. [Copyright &y& Elsevier]

Graphene conductive inks have attracted significant attention in recent years due to their high conductivity, corrosion resistance, and environmentally friendly nature. However, the dispersion of graphene in aqueous solution is still challenging. In this work, we synthesized an amphiphilic graft copolymer, polyvinyl alcohol-g-polyaniline (PVA-g-PANI), and studied the graphene dispersion prepared with the graft copolymer by high-speed shear dispersion. The amphiphilic graft copolymer can be used as a stabilizer and adhesive agent in graphene dispersion. Given the steric hindrance of the graft copolymer, the stability of graphene dispersion is improved by decreasing the probability of π–π stacking. PVA-g-PANI has a better stability on graphene dispersion than carboxymethylcellulose sodium (CMC-Na) and a mixture of PVA and PANI. The graft copolymer has only a slight effect on the conductivity of graphene dispersion due to the existence of conductive PANI, which is beneficial for preparing the graphene dispersion with good conductivity and adhesion. Graphene dispersion is well-adapted to screen printing and is very stable with regard to the sheet resistance bending cycle. [ABSTRACT FROM AUTHOR]

Abstract: In this study, rats were orally treated with the total saponins of Taraphochlamys affinis (TSTA) daily with administration of CCl4 twice a week for 8weeks. Compared to the normal control, CCl4 induced liver damage significantly increased the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in serum and decreased the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), and glutathione reductase (GSH-Rd) in liver. Meanwhile content of hepatic malondialdehyde (MDA), which was oxidative stress marker, was increased. Histological finding also confirmed the hepatotoxic characterization in rats. Furthermore, proinflammatory mediators including tumor necrosis factor-α(TNF-α) in serum, prostaglandin E2 (PGE2), inducible enitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in liver were detected with elevated contents, while expression of xenobiotic metabolizing enzyme – cytochrome P4502E1 (CYP2E1) was inhibited. The results revealed that TSTA not only significantly reversed CCl4 originated changes in serum toxicity and hepatotoxic characterization, but also altered expression of hepatic oxidative stress markers and proinflammatory mediators, combined with restoring liver CYP2E1 level. The results indicated that protective effect of TSTA against CCl4-induced hepatic injury may rely on its effect on reducing oxidative stress, suppressing inflammatory responses and improving drug-metabolizing enzyme activity in liver. [Copyright &y& Elsevier]

Abstract: A novel approach to the prediction of cutting temperatures within coated tools is presented in this paper. The diffusion layer that results thermal resistance between coating and its substrate is considered. The diffusion layer model was firstly developed. Equations for effective thermal conductivity of the diffusion layer were then derived based on three structural models such as the Maxwell–Eucken 1 model, the series model, and the equivalent layer model. The influences of diffusion layer on cutting temperatures of coated tools were analyzed. Results indicate that the calculated temperature with the new model is more accurate than that of the conventional one compared with measured temperature. The diffusion layer model developed in this work provides a methodology for the design and choice of coated tools in manufacturing industries. [Copyright &y& Elsevier]

Abstract: The cutting temperature during metal cutting processes has been recognized as one of major factors influencing the tool performance and workpiece geometry accuracy. This paper presents analyses of the one-dimensional transient temperature distributions in monolayer coated tools. The analytical formulae of the transient temperature distributions for the monolayer cutting tools are obtained using Laplace Transform. Computations of the temperature distributions in monolayer coated tools reveal that such factors as the coating material, substrate material and coating thickness have some influence on temperature distributions in monolayer coated tools. The present work provides some data for selecting appropriate coating materials to reduce temperature within coated tools. [Copyright &y& Elsevier]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Background. Hepatocellular carcinoma (HCC) is a high mortality malignant tumor with genetic and phenotypic heterogeneity, making predicting prognosis challenging. Meanwhile, the inflammatory response is an indispensable player in the tumorigenesis process and regulates the tumor microenvironment, which can affect the prognosis of tumor patients. Methods. Using HCC samples in the TCGA-LIHC dataset, we explored lncRNA expression profiles associated with the inflammatory response. The inflammatory response-related lncRNA signature was constructed by univariate Cox regression, LASSO regression, and multivariate Cox regression methods based on inflammatory response-related differentially expressed lncRNAs in HCC. Results. Seven inflammatory response-related lncRNA signatures were identified in predicting HCC prognosis. Kaplan–Meier (K-M) survival analysis indicated that high-risk group HCC patients were associated with poor prognosis. The utility of the inflammatory response-related lncRNA signatures was proved by the AUC and DCA analysis. The nomogram further confirmed the accuracy of the novel signature in predicting HCC patients' prognoses. In validation, our novel signature is more accurate than traditional clinicopathological performance for prognosis prediction of HCC patients. GSEA analysis further elucidated the underlying mechanisms and pathways of HCC progression in the low- and high-risk groups. Moreover, immune cells infiltration responses and immune function analyses revealed a significant difference between high- and low-risk groups in cytolytic activity, MHC class I, type I INF response, type II INF response, inflammation-promoting, and T cell coinhibition. Finally, HHLA2, NRP1, CD276, TNFRSF9, TNFSF4, CD80, and VTCN1 were expressed higher in high-risk groups in the immune checkpoint analysis. Conclusions. A novel inflammatory response-related lncRNA signature (AC145207.5, POLHAS1, AL928654.1, MKLN1AS, AL031985.3, PRRT3AS1, and AC023157.2) is capable of predicting the prognosis of HCC patients and providing new immune targeted therapies insight. [ABSTRACT FROM AUTHOR]

Carbon nanomaterials are unique with excellent functionality and diverse structures. However, agglomerated structures are commonly formed because of small‐size effects and surface effects. Their hierarchical assembly into micro particles enables carbon nanomaterials to break the boundaries of classical Geldart particle classification before stable fluidization under gas‐solid interactions. Currently, there are few systematic reports regarding the structural evolution and fluidization mechanism of carbon nano agglomerations. Based on existing research on carbon nanomaterials, this article reviews the fluidized structure control and fluidization principles of prototypical carbon nanotubes (CNTs) as well as their nanocomposites. The controlled agglomerate fluidization technology leads to the successful mass production of agglomerated and aligned CNTs. In addition, the self‐similar agglomeration of individual ultralong CNTs and nanocomposites with silicon as model systems further exemplify the important role of surface structure and particle‐fluid interactions. These emerging nano agglomerations have endowed classical fluidization technology with more innovations in advanced applications like energy storage, biomedical, and electronics. This review aims to provide insights into the connections between fluidization and carbon nanomaterials by highlighting their hierarchical structural evolution and the principle of agglomerated fluidization, expecting to showcase the vitality and connotation of fluidization science and technology in the new era. [ABSTRACT FROM AUTHOR]

Objective. To investigate the potential active ingredients and underlying mechanisms of Artemisia annua (AA) on the treatment of hepatocellular carcinoma (HCC) based on network pharmacology. Methods. In the present study, we used a network pharmacological method to predict its underlying complex mechanism of treating HCC. First, we obtained relative compounds of AA based on the traditional Chinese medicine systems pharmacology (TCMSP) database and collected potential targets of these compounds by target fishing. Then, we built HCC-related targets target by the oncogenomic database of hepatocellular carcinoma (OncoDB.HCC) and biopharmacological network (PharmDB-K) database. Based on the matching results between AA potential targets and HCC targets, we built a protein-protein interaction (PPI) network to analyze the interactions among these targets and screen the hub targets by topology. Furthermore, the function annotation and signaling pathways of key targets were performed by Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis using DAVID tools. Finally, the binding capacity between active ingredients and key targets was validated by molecular docking. Results. A total of 19 main active ingredients of AA were screened as target prediction; then, 25 HCC-related common targets were seeked out via multiple HCC databases. The areas of nodes and corresponding degree values of EGFR, ESR1, CCND1, MYC, EGF, and PTGS2 were larger and could be easily found in the PPI network. Furthermore, GO and KEGG enrichment analysis showed that these key targets were significantly involved in multiple biological processes and pathways which participated in tumor cell proliferation, apoptosis, angiogenesis, tumor invasion, and metastasis to accomplish the anti-HCC activity. The molecular docking analysis showed that quercetin could stably bind to the active pocket of EGFR protein 4RJ5 via LibDock. Conclusion. The anticancer effects of AA on HCC were predicted to be associated with regulating tumor cell proliferation, apoptosis, angiogenesis, tumor invasion, and metastasis via various pathways such as the EGFR signaling pathway, ESR1 signaling pathway, and CCND1 signaling pathway. It is suggested that AA might be developed as a broad-spectrum antitumor drug based on its characteristics of multicomponent, multipath, and multitarget. [ABSTRACT FROM AUTHOR]

The tissue stiffness of donor kidneys in transplantation may increase due to pathological changes such as glomerulosclerosis and interstitial fibrosis, and those changes associate worse outcomes in kidney transplantation recipients. Ultrasound elastography is a noninvasive imaging examination with the ability to quantitatively reflect tissue stiffness. Aim of this study was to evaluate the prognostic value of ultrasound elastography for adverse kidney outcome in kidney transplantation recipients. Shear wave elastography (SWE) examinations were performed by two independent operators in kidney transplantation recipients. The primary outcome was a composite of kidney graft deterioration, all-cause re-hospitalization, and all-cause mortality. Survival analysis was calculated by Kaplan-Meier curves with the log-rank test and Cox regression analysis. A total of 161 patients (mean age 46 years, 63.4% men) were followed for a median of 20.1 months. 27 patients (16.77%) reached the primary endpoint. The mean and median tissue stiffness at the medulla (hazard ratio: 1.265 and 1.229, respectively), estimated glomerular filtration rate (eGFR), and serum albumin level were associated with the primary outcome in univariate Cox regression. Adding mean or median medulla SWE to a baseline model containing eGFR and albumin significantly improved its discrimination (C-statistics: 0.736 for the baseline, 0.766 and 0.772 for the model added mean and median medulla SWE, respectively). The medullary tissue stiffness of kidney allograft measured by shear wave elastography may provide incremental prognostic value to adverse outcomes in kidney transplantation recipients. Including SWE parameters in kidney transplantation recipients management could be considered to improve risk stratification. [ABSTRACT FROM AUTHOR]

Background. mTORC1 signal pathway plays a role in the initiation and progression of hepatocellular carcinoma (HCC), but no relevant gene signature was developed. This research aimed to explore the potential correlation between the mTORC1 signal pathway and HCC and establish the related gene signature. Methods. HCC cases were retrieved from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) databases. The genes included in mTORC1-associated signature were selected by performing univariate and multivariate Cox regression analyses and lasso regression analysis. The protein expression level of included genes was verified by The Human Protein Altas. Then, the signature was verified by survival analysis and multiple receiver operating characteristic (ROC) curve. Moreover, the correlation between signature and immune cells infiltration was investigated. Furthermore, a nomogram was established and evaluated by C-index and calibration plot. Results. The signature was established with the six genes (ETF1, GSR, SKAP2, HSPD1, CACYBP, and PNP). Three genes (ETF1, GSR, and HSPD1) have verified their protein expression level in HCC. Under the grouping from signature, patients in the high-risk group showed worse survival than those in the low-risk group in both three datasets. The signature was found to be significantly associated with the infiltration of B cells, CD4+ T-cells, CD8+ T-cells, dendritic cells, macrophages, and neutrophils. The univariate and multivariate Cox regression analysis indicated that mTORC1-related signature could be the potential independent prognostic factor in HCC. Finally, the nomogram involving age, gender, stage, and signature has been established and verified. Conclusion. The mTORC1-associated gene signature established and validated in our research could be used as a potential prognostic factor in HCC. [ABSTRACT FROM AUTHOR]

Background: Malignant glioma is refractory to conventional treatment, highlighting a need to develop novel efficacious therapies. Biguanides, a class of oral antidiabetic drug, have been thought to inhibit proliferation and metastasis in a variety of cancers. Purpose: The objective of this study was to investigate the affections of biguanides, phenformin (Phen) and metformin (Met), on growth and migration of glioma cells LN229 in vitro and in vivo. Methods: Glioma cells LN229 were treated with Phen or Met, then cell proliferation and death were evaluated by MTT assay and PI stain, and cell cycle were evaluated using flow cytometric analysis, meantime wound healing assay and transwell migration assay were performed to detect cell migration ability. In addition, LN229 were injected in thigh of nude mice, and the mice were treated with Phen or Met to detect the effect of Phen and Met in vivo. Results: Phen and Met could significantly inhibit cell growth through inhibiting cell proliferation, promoting cell death and disturbing cell cycle, and these drugs also could inhibit cell colony formation in glioma cells LN229 in vitro. Meanwhile, both Phen and Met could significantly inhibit cell migration of LN229 in vitro, through effecting the expression of E-cadherin and Vimentin. In addition, both Phen and Met inhibited the growth and migration of LN229 in a tumor xenograft model. Furthermore, Phen and Met were associated with the increased level of ROS of cell mitochondrial, and ROS inhibitor NAC could significantly rescue the cell death induced by Phen and Met. Conclusion: Phen and Met displayed powerful antitumor effects of LN229, and our findings powerfully suggest the possibility of Phen and Met being used as an adjuvant agent in the treatment of glioma patients. [ABSTRACT FROM AUTHOR]

A microporous MgO–MgAl 2 O 4 gas-permeable brick was fabricated for use in tundish to remove small inclusions in liquid steel using argon bubbles, based on the optimization of particle gradation. The effect of activated alumina addition on the properties and pore size distribution of microporous MgO–MgAl 2 O 4 bricks was investigated. The flow rate parameters of argon for inclusion removal were optimized. The results showed that the microporous MgO–MgAl 2 O 4 permeable brick, prepared by adding 5 wt% activated alumina, had a minimum average pore diameter of 10.9 μm and greater air permeability compared to no introduction of activated alumina. The thermal stability was significantly improved due to the long cone-shaped magnesium-rich spinels generated by the solid-state reaction between magnesium oxide and activated alumina distributed in the pores; this further remodeled the structure of the pores. The addition of more activated alumina caused a sharp drop in the volume density and strength and formed more spinels, with the morphology of spinels changing from long cone to octahedron with larger average pore size; these are not beneficial to the production and application of gas-permeable brick. When the flow rate was 60 L/min, the total oxygen content (T.[O]) in the billet was reduced by 7 ppm, the content of pores and cracks in the billet decreased dramatically, and the removal rates of inclusion size distributions of 20–50 μm, 50–100 μm, and >100 μm in the billets increased by 15%, 20%, and 61%, respectively. [ABSTRACT FROM AUTHOR]

Tengfu Jiangya Tablet (TJT) is a well accepted antihypertension drug in China and its major active components were Uncaria total alkaloids and Semen Raphani soluble alkaloid. To further explore treatment effects mechanism of TJT on essential hypertension, a serum proteomic study was performed. Potential biomarkers were quantified in serum of hypertension individuals before and after taking TJT with isobaric tags for relative and absolute quantitation (iTRAQ) coupled two-dimensional liquid chromatography followed electrospray ionization-tandem mass spectrometry (2D LC-MS/MS) proteomics technique. Among 391 identified proteins with high confidence, 70 proteins were differentially expressed (fold variation criteria, >1.2 or <0.83) between two groups (39 upregulated and 31 downregulated). Combining with Gene Ontology annotation, KEGG pathway analysis, and literature retrieval, 5 proteins were chosen as key target biomarkers during TJT therapeutic process. And the alteration profiles of these 5 proteins were verified by ELISA and Western Blot. Proteins Kininogen 1 and Keratin 1 are members of Kallikrein system, while Myeloperoxidase, Serum Amyloid protein A, and Retinol binding protein 4 had been reported closely related to vascular endothelial injury. Our study discovered 5 target biomarkers of the compound Chinese medicine TJT. Secondly, this research initially revealed the antihypertension therapeutic mechanism of this drug from a brand-new aspect. [ABSTRACT FROM AUTHOR]

The taxonomy of Reticulitermes Holmgren (Isoptera: Rhinotermitidae) in China is problematic and in need of revision. Most Chinese Reticulitermes species were described in the 1980s and 1990s, and have never been studied since then. In this study, morphological characteristics including coloration, pilosity, shape, and morphometric characteristics of Reticulitermes dichrous Ping and Reticulitermes guangzhouensis Ping were compared. In addition, a portion of the ribosomal RNA large subunit 16S ( 16S rRNA) and the mitochondrial DNA cytochrome oxidase subunit II ( COII) genes from different populations of the 2 species were sequenced and analyzed. Morphological comparisons revealed the similarities between the 2 species in both discrete and morphometric characteristics. In the molecular phylogenetic trees inferred from COII and 16S rRNA genes, all of the examined populations of the 2 species clustered into a common clade with a high bootstrap value. Based on the morphological comparisons and the molecular analyses, it is proposed that R. dichrous is a junior synonym of R. guangzhouensis. [ABSTRACT FROM AUTHOR]

Background: Liver carcinoma generally presents as an immunosuppressive microenvironment that promotes tumor evasion. The intercellular crosstalk of immune cells significantly influences the construction of an immunosuppressive microenvironment. This study aimed to investigate the important interactions between immune cells and their targeting drugs in liver carcinoma, by using single-cell and bulk transcriptomic data.Methods: Single-cell and bulk transcriptomic data were retrieved from Gene Expression Omnibus (GSE159977, GSE136103, and GSE125449) and The Cancer Genome Atlas (TGCA-LIHC), respectively. Quality control, dimension reduction, clustering, and annotation were performed according to the Scanpy workflow based on Python. Cell-cell interactions were explored using the CellPhone database and CellChat. Trajectory analysis was executed using a partition-based graph abstraction method. The transcriptomic factors (TFs) were predicted using single-cell regulatory network inference and clustering (SCENIC). The target genes from TFs were used to establish a related score based on the TCGA cohort; this score was subsequently validated by survival, gene set enrichment, and immune cell infiltration analyses. Drug prediction was performed based on the Cancer Therapeutics Response Portal and PRISM Repurposing datasets.Results: Thirty-one patients at four different states, including health, hepatitis, cirrhosis, and cancer, were enrolled in this study. After dimension reduction and clustering, twenty-two clusters were identified. Cell-cell interaction analyses indicated that macrophage-naive CD4 + T cell interaction significantly affect cancerous state. In brief, macrophages interact with naive CD4 + T cells via different pathways in different states. The results of SCENIC indicated that macrophages present in cancer cells were similar to those present during cirrhosis. A macrophage-naive CD4 + T cell (MNT) score was generated by the SCENIC-derived target genes. Based on the MNT score, five relevant drugs (inhibitor of polo-like kinase 1, inhibitor of kinesin family member 11, dabrafenib, ispinesib, and epothilone-b) were predicted.Conclusions: This study reveals the crucial role of macrophage-naive CD4 + T cell interaction in the immunosuppressive microenvironment of liver carcinoma. Tumor-associated macrophages may be derived from cirrhosis and can initiate liver carcinoma. Predictive drugs that target the macrophage-naive CD4 + T cell interaction may help to improve the immunosuppressive microenvironment and prevent immune evasion. The relevant mechanisms need to be further validated in experiments and cohort studies. [ABSTRACT FROM AUTHOR]

Simple Summary: The use of diverse omics platforms and small sample sizes in current studies of cancer chemoresistance limits consensus regarding the molecular mechanisms underlying chemoresistance and the applicability of those study findings. We built transcriptome data for chemotherapy-resistant breast cancer samples for two cohorts and conducted pathway and subpathway analyses that revealed the activation of several molecular pathways associated with chemoresistance in Cushing's syndrome, human papillomavirus infection, proteoglycans in cancer, fluid shear stress, and focal adhesion that have not been reported in the resistance of breast cancer to chemotherapy. However, analysis of a subset of triple-negative breast cancer samples revealed activation of the identical chemoresistance pathways. Chemoresistance has been a major challenge in the treatment of patients with breast cancer. The diverse omics platforms and small sample sizes reported in the current studies of chemoresistance in breast cancer limit the consensus regarding the underlying molecular mechanisms of chemoresistance and the applicability of these study findings. Therefore, we built two transcriptome datasets for patients with chemotherapy-resistant breast cancers—one comprising paired transcriptome samples from 40 patients before and after chemotherapy and the second including unpaired samples from 690 patients before and 45 patients after chemotherapy. Subsequent conventional pathway analysis and new subpathway analysis using these cohorts uncovered 56 overlapping upregulated genes (false discovery rate [FDR], 0.018) and 36 downregulated genes (FDR, 0.016). Pathway analysis revealed the activation of several pathways in the chemotherapy-resistant tumors, including those of drug metabolism, MAPK, ErbB, calcium, cGMP-PKG, sphingolipid, and PI3K-Akt, as well as those activated by Cushing's syndrome, human papillomavirus (HPV) infection, and proteoglycans in cancers, and subpathway analysis identified the activation of several more, including fluid shear stress, Wnt, FoxO, ECM-receptor interaction, RAS signaling, Rap1, mTOR focal adhesion, and cellular senescence (FDR < 0.20). Among these pathways, those associated with Cushing's syndrome, HPV infection, proteoglycans in cancer, fluid shear stress, and focal adhesion have not yet been reported in breast cancer chemoresistance. Pathway and subpathway analysis of a subset of triple-negative breast cancers from the two cohorts revealed activation of the identical chemoresistance pathways. [ABSTRACT FROM AUTHOR]

Background: Adverse events induced by drug-drug interactions are a major concern in the United States. Current research is moving toward using electronic health record (EHR) data, including for adverse drug events discovery. One of the first steps in EHR-based studies is to define a phenotype for establishing a cohort of patients. However, phenotype definitions are not readily available for all phenotypes. One of the first steps of developing automated text mining tools is building a corpus. Therefore, this study aimed to develop annotation guidelines and a gold standard corpus to facilitate building future automated approaches for mining phenotype definitions contained in the literature. Furthermore, our aim is to improve the understanding of how these published phenotype definitions are presented in the literature and how we annotate them for future text mining tasks. Results: Two annotators manually annotated the corpus on a sentence-level for the presence of evidence for phenotype definitions. Three major categories (inclusion, intermediate, and exclusion) with a total of ten dimensions were proposed characterizing major contextual patterns and cues for presenting phenotype definitions in published literature. The developed annotation guidelines were used to annotate the corpus that contained 3971 sentences: 1923 out of 3971 (48.4%) for the inclusion category, 1851 out of 3971 (46.6%) for the intermediate category, and 2273 out of 3971 (57.2%) for exclusion category. The highest number of annotated sentences was 1449 out of 3971 (36.5%) for the "Biomedical & Procedure" dimension. The lowest number of annotated sentences was 49 out of 3971 (1.2%) for "The use of NLP". The overall percent inter-annotator agreement was 97.8%. Percent and Kappa statistics also showed high inter-annotator agreement across all dimensions. Conclusions: The corpus and annotation guidelines can serve as a foundational informatics approach for annotating and mining phenotype definitions in literature, and can be used later for text mining applications. [ABSTRACT FROM AUTHOR]

Background: Adverse events induced by drug-drug interactions are a major concern in the United States. Current research is moving toward using electronic health record (EHR) data, including for adverse drug events discovery. One of the first steps in EHR-based studies is to define a phenotype for establishing a cohort of patients. However, phenotype definitions are not readily available for all phenotypes. One of the first steps of developing automated text mining tools is building a corpus. Therefore, this study aimed to develop annotation guidelines and a gold standard corpus to facilitate building future automated approaches for mining phenotype definitions contained in the literature. Furthermore, our aim is to improve the understanding of how these published phenotype definitions are presented in the literature and how we annotate them for future text mining tasks. Results: Two annotators manually annotated the corpus on a sentence-level for the presence of evidence for phenotype definitions. Three major categories (inclusion, intermediate, and exclusion) with a total of ten dimensions were proposed characterizing major contextual patterns and cues for presenting phenotype definitions in published literature. The developed annotation guidelines were used to annotate the corpus that contained 3971 sentences: 1923 out of 3971 (48.4%) for the inclusion category, 1851 out of 3971 (46.6%) for the intermediate category, and 2273 out of 3971 (57.2%) for exclusion category. The highest number of annotated sentences was 1449 out of 3971 (36.5%) for the "Biomedical & Procedure" dimension. The lowest number of annotated sentences was 49 out of 3971 (1.2%) for "The use of NLP". The overall percent inter-annotator agreement was 97.8%. Percent and Kappa statistics also showed high inter-annotator agreement across all dimensions. Conclusions: The corpus and annotation guidelines can serve as a foundational informatics approach for annotating and mining phenotype definitions in literature, and can be used later for text mining applications. [ABSTRACT FROM AUTHOR]

The rapid development of the Internet of Things (IoT) has accelerated the integration of science and technology with life, enabling the public to start enjoying the convenience brought by intelligent living. However, there are multiple resource-constrained sensing devices in IoT, which are always facing various external or internal attacks, making it difficult to ensure the secure transmission of sensitive data in IoT. Therefore, to address the problem of data transmission in resource-constrained devices in IoT, we propose a new certificateless hybrid signcryption scheme for IoT. It is a novel scheme that satisfies confidentiality and unforgeability, showing higher computational efficiency and lower overhead of transmission. To prove that it satisfies the efficent transmission of IoT, we conduct simulation experiments, and the experimental results show that our proposed scheme has higher efficiency than the existing schemes. [ABSTRACT FROM AUTHOR]

Abstract: This study was designed to investigate the protective effects of the methyl helicterate (MH) isolated from Helicteres angustifolia L. against CCl4-induced hepatotoxicities in rats. Liver injury was induced in rats by the administration of CCl4 twice a week for 8weeks. Compared with the CCl4 group, MH significantly decreased the activities of ALT, AST and ALP in the serum and increased the activities of SOD, GSH-Px and GSH-Rd in the liver. Moreover, the content of hepatic MDA was reduced. Histological findings also confirmed the anti-hepatotoxic characterisation. In addition, MH significantly inhibited the proinflammatory mediators, such as PGE2, iNOS, COX-2, IL-6, TNF-α and myeloperoxidase (MPO). Further investigation showed that the inhibitory effect of MH on the proinflammatory cytokines was associated with the downregulation of NF-κB. Besides, MH also markedly decreased the levels of Fas/FasL protein expression and the activities of caspase-3/8, as well as the activity of cytochrome P4502E1 (CYP2E1). In brief, the protective effect of MH against CCl4-induced hepatic injury may rely on its ability to reduce oxidative stress, suppress inflammatory responses, protect against Fas/FasL-mediated apoptosis and block CYP2El-mediated CCl4 bioactivation. [Copyright &y& Elsevier]

Simple Summary: Mikania micrantha Kunth is among the most invasive weeds in the world, causing extensive damage to both natural ecosystems and agroforestry systems. Mechanical removal is one of the most effective and straightforward approaches to controlling this weed, but this results in extensive lignocellulosic waste, and effective approaches to exploiting this abundant biomass are limited. Coptotermes formosanus Shiraki is not only an important subterranean termite pest species but also a considerable decomposer with the ability to digest lignocellulose. In this study, we evaluated the effects of a diet composed of M. micrantha leaves on C. formosanus workers. The workers increased their dietary intake when fed M. micrantha leaves, with a concomitant gradual increase in mortality rate. From the metabolic profiles, changes in metabolites and their related metabolic pathways suggested that termites can utilize M. micrantha-derived lignocellulose, but their antioxidant activity and signal transduction may be suppressed. Overall, this study identified key metabolites and pathways associated with the response of these termites to dietary changes and the effect of M. micrantha on termites. Effective approaches to exploiting the biomass of the abundant invasive weed Mikania micrantha Kunth are limited. Termites have been a focus of significant attention as mediators of biomass-processing owing to their ability to digest lignocellulose. Here, the GC/TOF-MS approach was employed to assess the effects of a diet composed of M. micrantha leaves on Coptotermes formosanus workers, with the growth performance of these workers also being assessed. The workers increased their dietary intake when fed M. micrantha leaves, with a concomitant gradual increase in mortality rate. A total of 62 differentially abundant metabolites and nine significantly affected pathways were found when comparing termites fed M. micrantha leaves to pinewood. Key metabolites, including carbohydrates, polyols, 4-hydroxyphenylacetic acid, and their related metabolic pathways, suggested that termites can digest and utilize M. micrantha-derived lignocellulose. However, changes in the tryptophan metabolism, tyrosine metabolism, and sphingolipid metabolism suggest an adverse effect of M. micrantha leaves on antioxidant activity and signal transduction in termites. Overall, this study identified the key metabolites and pathways associated with the response of these termites to dietary changes and the effect of M. micrantha on termites. [ABSTRACT FROM AUTHOR]

To explore a low–cost functional phase alternative material for thick film resistors, the thermal behavior, sintering and electrical properties of LaCo 0·4 Ni 0.6-y Zn y O 3 (y = 0.00–0.08, LCNZ) ceramics were investigated through experiments and density functional theory calculations. Results of simultaneous thermal analysis, thermomechanical analysis, scanning electron microscopy, and DC four–probe method indicated that substitution of Ni-ion by Zn–ion could lower the phase formation and densification temperatures of LCNZ, as well as increase the resistivity and decrease the temperature coefficient of resistance (TCR). The resistivity of 0.94 mΩ cm (y = 0.00) and 1.03 mΩ cm (y = 0.02), as well as TCR value of −312.79 ppm/°C (for y = 0.00) and −872.82 ppm/°C (for y = 0.02) could be achieved as the LCNZ ceramics sintered at 1200 °C. The variations of octahedral bond population, electron density around oxygens, and partial density of states near the Fermi level firmly supported the results of experiments. [ABSTRACT FROM AUTHOR]

Aims. Abundant evidences in traditional Chinese medicine (TCM) supported the therapeutic value of herbal medicine Yinchen in hepatocellular carcinoma (HCC), but the underlying mechanism remains to be investigated. Main Methods. The intersection of immune gene set, module genes, HCC-associated genes, and target genes of Yinchen was employed for further analyses. The module genes were identified by weighted gene coexpression network analysis, and the other three gene sets were obtained from public databases. Subsequently, we further explored the clinical value and immunoregulation of the hub gene of intersection. The relevant pathways related to hub gene expression were investigated by gene set enrichment analysis. Finally, the interaction of active compounds and target genes was validated by molecular docking. Key Findings. Thirteen active compounds and 90 target genes of Yinchen were included. After constructing the network among Yinchen, target genes, and HCC, BIRC5 was identified as the hub gene. Significant difference was found between the high-expressed group and the low-expressed group in survival and stage. Different immune subtypes also presented significant difference in BIRC5 expression. Moreover, NK cell and T cell (CD4+ effector memory and CD4+ memory resting) were negatively correlated with BIRC5 expression, while CTLA4 and LAG3 were positively correlated. The results of molecular docking further validated a good binding activity of quercetin-BIRC5 interaction. Significance. In summary, our research identified for the first time a novel underlying association among herbal medicine Yinchen, BIRC5, immunotherapy, and HCC. We speculated that Yinchen may target the immune checkpoints (CTLA4 and LAG3) and activate the immune cells by suppressing BIRC5. [ABSTRACT FROM AUTHOR]

Simple Summary: Pseudorabies virus (PRV) is a common pathogen in multiple animal species, particularly in pigs, which is now one of the most important factors on pig husbandry loss. This study isolated a PRV variation strain HNXY and performed the etiology characterization of HNXY. Moreover, the attenuated rHNXY-∆TK/∆gE presented satisfactory safety among susceptible animals, which It is worthy of doing more studies on this variation strain as PRV vaccine candidate. The outbreak of pseudorabies in China, caused by more virulent pseudorabies virus (PRV) than the classical strains, has led to considerable economic losses. In this study, PRV strain HNXY was isolated from the Henan province of China in 2015 from the pig farm with severe reproductive failure in sows and a high mortality in piglets. The 50% tissue culture infectious doses (TCID50) of HNXY in Vero cells were examined to be 106.5/mL, and the neutralisation titer against Bartha-K61 was significantly higher than against HNXY when tested with the serum from Bartha-K61 vaccinated pigs. The 50% lethal doses (LD50) of HNXY to six-week-old BALB/c mice and two-month-old PRV-free pigs were both 102.3 TCID50. HNXY was classified as genotype II, and numerous amino acid variations were found in gB, gE, gC, gD, TK, and RR1 proteins, compared with PRV from other countries or those prevalent in China before 2012. The attenuated rHNXY-∆TK/∆gE was further constructed, which presented significantly smaller plaques than HNXY, as well as the similar growth kinetics. rHNXY-∆TK/∆gE was confirmed to be non-pathogenic to six-week-old BALB/c mice and zero-day-old piglets. This study isolated updated PRV promising to develop into a new vaccine candidate. [ABSTRACT FROM AUTHOR]

• DHA alleviated PA-induced cytotoxicity in cardiomyoblast cells. • DHA ameliorated the progression of cardiomyopathy in a HFD-fed rat model of diabetes. • DHA improved palmitate-induced mitochondrial dysfunction both in vivo and in vitro. Regular consumption of n-3 polyunsaturated fatty acids is associated with decreased cardiovascular morbidity and mortality. This study assessed the therapeutic effect of docosahexaenoic acid (DHA) in palmitic acid (PA)-induced cytotoxicity in vitro and in rats fed a high-fat diet (HFD). H9C2 cells and rat primary cardiomyoblasts were exposed to PA or PA + DHA for 24 h. PA-induced lipotoxicity and mitochondrial dysfunction were evaluated by immunostaining, real-time PCR, cardiomyocyte contraction and transmission electron microscopy. The effects of dietary DHA on diabetic cardiomyopathy were evaluated in male Sprague-Dawley rats fed a reference diet rich in DHA, an HFD, or an HFD with added DHA for 16 weeks. Oxidative stress and lipotoxicity in rat heart tissue were assayed by Masson staining, immunohistochemistry, and TUNEL. In vitro studies showed that dietary DHA reduced the occurrence of cardiomyopathy and improved cardiac responses to PA. In the rat model, dietary DHA reduced mitochondrial oxidative stress in HFD-induced diabetic cardiomyopathy. Dietary DHA reduced mitochondrial oxidative stress and ameliorated PA-induced lipid toxicity. DHA consumption may have had direct effects on cardiovascular risk via myocardial protection. [ABSTRACT FROM AUTHOR]

Background. Accumulating evidence from prospective epidemiological studies has showed that depression disorder (DD) is a risk factor for cancer. The aim of this study is to explore the association of DD and the overall occurrence risk of hepatocellular carcinoma (HCC) and the mechanism. Methods. In this study, 60 mice were randomly divided into four groups: Control group, DD group, HCC group, HCC-DD group. Mice received a chronic dose of reserpine to establish depression model, followed by Diethylnitrosamine and Carbon tetrachloride administration to establish HCC models. Behavioral depression was assessed by sucrose preference test (SPT) and the expression of Serotonin 1A (5-HT1A) receptor in the hippocampal. The expression of Oatp2a1 and Oatp2b1 in the digestive system tissues was detected by PCR and western blotting. Results. Reserpine-administrated mice had a reducing sucrose preference at Day 14 compared with blank mice (P<0.05). The expression of 5-HT1A receptor in the hippocampal was decreased in DD mice compared with blank mice. The survival analysis indicated that the HCC mice with DD have poorer survival rate compared with the HCC mice. Compared with HCC mice, the expression of Oatp2a1 and Oatp2b1 was lower in liver and stomach tissue and higher in hepatic carcinoma and colon tissue of HCC-DD mice (P<0.05), and the expression of Oatp2a1 was higher in the spleen tissue of HCC-DD mice while the expression of Oatp2b1 was lower (P<0.05). However, no difference was found in the expression of Oatp2a1 and Oatp2b1 in the small intestine tissue between HCC group and HCC-DD group. Conclusions. DD was the adverse factors for the overall occurrence risk of HCC. Mechanistically, be the downregulation of Oatp2a1 and Oatp2b1 in liver tissue induced by DD might be involved. [ABSTRACT FROM AUTHOR]

Drug metabolites (DMs) are critical in pharmacology research areas, such as drug metabolism pathways and drug‐drug interactions. However, there is no terminology dictionary containing comprehensive drug metabolite names, and there is no named entity recognition (NER) algorithm focusing on drug metabolite identification. In this article, we developed a novel NER system, DrugMetab, to identify DMs from the PubMed abstracts. DrugMetab utilizes the features characterized from the Part‐of‐Speech, drug index, and pre/suffix, and determines DMs within context. To evaluate the performance, a gold‐standard corpus was manually constructed. In this task, DrugMetab with sequential minimal optimization (SMO) classifier achieves 0.89 precision, 0.77 recall, and 0.83 F‐measure in the internal testing set; and 0.86 precision, 0.85 recall, and 0.86 F‐measure in the external validation set. We further compared the performance between DrugMetab and whatizitChemical, which was designed for identifying small molecules or chemical entities. DrugMetab outperformed whatizitChemical, which had a lower recall rate of 0.65. [ABSTRACT FROM AUTHOR]

In the present work, the uniaxial deformation of 1-hexene based Linear Low Density Polyethylene (LLDPE) cast film at slow to very fast stretching speed (initial strain rate 10 −3 to 8.3 s −1 ) was investigated, together with a high speed video camera for capturing craze morphologies. The structural evolution of the deformed film at different speeds was also studied with Small Angle X-ray Scattering. Very different tensile behavior is observed when the film is stretched at very fast speed. Voids are detected by SAXS for slow MD and TD stretching processes; but no visible crazes are observed. However, visible crazes appear starting at a small satrain of 0.3 during fast MD stretching, due to the film being more rigid when stretched at the fast speed. The crazes appear with the length direction being perpendicular to the stretching direction and propagate quickly in the length direction. The crazes appear almost everywhere in the film during the fast MD stretching, while only occur in the central region during the fast TD stretching due to the preferred crystal orientation in MD direction where crazes can propagate more easily and faster. The structure transition at lamellar level is much faster during the fast stretching process, due to the formation of the visible crazes. The leaning is helpful for better understanding puncture, dart and tear tests of PE films, where the films undergo the fast deformation. [ABSTRACT FROM AUTHOR]

Summary The NatB N-terminal acetyltransferase specifically acetylates the N-terminal group of substrate protein peptides starting with Met-Asp/Glu/Asn/Gln. How NatB recognizes and acetylates these substrates remains unknown. Here, we report crystal structures of a NatB holoenzyme from Candida albicans in the presence of its co-factor CoA and substrate peptides. The auxiliary subunit Naa25 of NatB forms a horseshoe-like deck to hold specifically its catalytic subunit Naa20. The first two amino acids Met and Asp of a substrate peptide mediate the major interactions with the active site in the Naa20 subunit. The hydrogen bonds between the substrate Asp and pocket residues of Naa20 are essential to determine the NatB substrate specificity. Moreover, a hydrogen bond between the amino group of the substrate Met and a carbonyl group in the Naa20 active site directly anchors the substrate toward acetyl-CoA. Together, these structures define a unique molecular mechanism of specific N-terminal acetylation acted by NatB. [ABSTRACT FROM AUTHOR]

We used a porcine model of acute myocardial infarction to study the signal evolution of ischemic myocardium on diffusion-weighted magnetic resonance images (DWI). Eight Chinese miniature pigs underwent percutaneous left anterior descending or left circumflex coronary artery occlusion for 90 minutes followed by reperfusion, which induced acute myocardial infarction. We used DWI preprocedurally and hourly for 4 hours postprocedurally. We acquired turbo inversion recovery magnitude T2-weighted images (TIRM T2WI) and late gadolinium enhancement images from the DWI slices. We measured the serum myocardial necrosis markers myoglobin, creatine kinase-MB isoenzyme, and cardiac troponin I at the same time points as the magnetic resonance scanning. We used histochemical staining to confirm injury. All images were analyzed qualitatively. Contrast-to-noise ratio (the contrast between infarcted and healthy myocardium) and relative signal index were used in quantitative image analysis. We found that DWI identified myocardial signal abnormity early (<4 hr) after acute myocardial infarction and identified the infarct-related high signal more often than did TIRM T2WI: 7 of 8 pigs (87.5%) versus 3 of 8 (37.5%) ( P=0.046). Quantitative image analysis yielded a significant difference in contrast-to-noise ratio and relative signal index between infarcted and normal myocardium on DWI. However, within 4 hours after infarction, the serologic myocardial injury markers were not significantly positive. We conclude that DWI can be used to detect myocardial signal abnormalities early after acute myocardial infarction-identifying the infarction earlier than TIRM T2WI and widely used clinical serologic biomarkers. [ABSTRACT FROM AUTHOR]

Aims/Introduction This study was to assess the association between serum osteocalcin level and glucose metabolism in a Chinese male population. Materials and Methods We carried out a cross-sectional study with a cohort of participants from the Fangchenggang Area Male Health and Examination Survey. The cross-sectional study was carried out among 2,353 men, including 2,139 participants with normal glucose tolerance, 148 with impaired fasting glucose and 66 with type 2 diabetes. A subsample of 1,109 men with measurement of osteocalcin was observed in the cohort. After a 4-year follow-up period, 1,049 non-diabetic and 983 participants with normal glucose tolerance who submitted the available information were enrolled in the cohort. Participants were divided into group-H (≥23.33 ng/ mL) and group-L (<23.33 ng/mL) by osteocalcin level. Results In the cross-sectional study, osteocalcin levels were highest in participants with normal glucose tolerance, followed by those with impaired fasting glucose and type 2 diabetes ( P < 0.001). In partial correlation analysis adjusted for age, serum osteocalcin level was related to glucose level ( r = −0.082, P < 0.001), insulin level ( r = −0.079, P < 0.001) and insulin resistance ( r = −0.065, P = 0.002). Compared with group-H, group-L was associated with an increased risk of type 2 diabetes (odds ratio 2.107, 95% confidence interval 1.123-3.955), impaired fasting glucose (odds ratio 2.106; 95% CI 1.528-2.902), and insulin resistance (odds ratio 1.359, 95% confidence interval 1.080-1.710) adjusted for age, education levels, cigarette smoking and lipid profiles. In the cohort study, the increased risk of impaired fasting glucose was significant in group-L vs group-H (3.3% vs 1.2%, P = 0.026). Conclusions Low serum osteocalcin level was a risk factor for impaired glucose metabolism and subsequent type 2 diabetes. [ABSTRACT FROM AUTHOR]

We have recently developed a bivalent strategy to provide novel compounds that potentially target multiple risk factors involved in the development of Alzheimer's disease (AD). Our previous studies employing a bivalent compound with a shorter spacer (17MN) implicated that this compound can localize into mitochondria and endoplasmic reticulum (ER), thus interfering with the change of mitochondria membrane potential (MMP) and Ca2+ levels in MC65 cells upon removal of tetracycline (TC). In this report, we examined the effects by a bivalent compound with a longer spacer (21MO) in MC65 cells. Our results demonstrated that 21MO suppressed the change of MMP, possibly via interaction with the mitochondrial complex I in MC65 cells. Interestingly, 21MO did not show any effects on the Ca2+ level upon TC removal in MC65 cells. Our previous studies suggested that the mobilization of Ca2+ in MC65 cells, upon withdraw of TC, originated from ER, so the results implicated that 21MO may preferentially interact with mitochondria in MC65 cells under the current experimental conditions. Collectively, the results suggest that bivalent compounds with varied spacer length and cell membrane anchor moiety may exhibit neuroprotective activities via different mechanisms of action. [ABSTRACT FROM AUTHOR]

The drywood termite Cryptotermes domesticus is an important worldwide pest with limited genomic resources that causes substantial damage to dry timber and structural lumber. Here, we performed transcriptome sequencing for Cr. domesticus pseudergate using Illumina paired-end sequencing technology. A total of 108,745,470 clean reads were collected and assembled into 302,979 contigs with an average length of 648 bp and an N50 length of 893 bp. A total of 185,248 unigenes and 100,680 proteins were identified among the assembled contigs. Of these, there were 152,317 (50.27%) contigs with significant similarity to publicly available databases. To understand how the termites respond to phylogenetically diverse wood species, variations in gene expression were examined among pseudergates feeding on three wood species from different plant families, Casuarina equisetifolia (CE), Koompassia excelsa (KE) and Myristica sp . (MS). A total of 417 (118 up-regulated/299 down-regulated), 599 (148 up-regulated/451 down-regulated) and 505 (223 up-regulated/282 down-regulated) differentially expressed genes were detected in KE vs. CE, KE vs. MS and CE vs. MS, respectively. Digital gene expression analysis indicated that different wood species played an important role in the expression of termite genes, such as genes involved in carbohydrate metabolism, and proteins with catalytic activity and hydrolase activity. Additionally, the genes encoding cellulase were identified and analyzed. This study provides the first primary transcriptome of Cr. domesticus and lays a foundation for future functional genomics studies in the feeding responses. [ABSTRACT FROM AUTHOR]

Traditional Chinese Medicine Jianpijiedu decoction (JPJD) could improve the general status of liver cancer patients in clinics, especially the symptoms of decreased food intake and diarrhea. In this study, our results showed that the survival rate of the liver cancer with food restriction and diarrhea (FRD-LC) rats was lower than the liver cancer (LC) rats, and the tumor volume of the FRD-LC rats was higher than the LC rats. It was also shown that the high dose of JPJD significantly improved the survival rate, weight, and organ weight when compared with FRD-LC-induced rats. Moreover, JPJD administration upregulated the mRNA and protein levels of ABCC2 and downregulated the mRNA and protein levels of OATP1B2 in liver tissues. However, opposite results were observed in the cancer tissues. In conclusion, the study indicated that the Chinese Medicine JPJD could contribute to the rats with liver cancer which were pretreated with food restriction and diarrhea by regulating the expression of ABCC2 and OATP1B2 in liver tissues and cancer tissues. [ABSTRACT FROM AUTHOR]